WO2009060063A1 - Anthelmintic combination - Google Patents
Anthelmintic combination Download PDFInfo
- Publication number
- WO2009060063A1 WO2009060063A1 PCT/EP2008/065126 EP2008065126W WO2009060063A1 WO 2009060063 A1 WO2009060063 A1 WO 2009060063A1 EP 2008065126 W EP2008065126 W EP 2008065126W WO 2009060063 A1 WO2009060063 A1 WO 2009060063A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- ivermectin
- trichlorfon
- abamectin
- albendazole
- sulphoxide
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
- C07D235/30—Nitrogen atoms not forming part of a nitro radical
- C07D235/32—Benzimidazole-2-carbamic acids, unsubstituted or substituted; Esters thereof; Thio-analogues thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
- A61K31/662—Phosphorus acids or esters thereof having P—C bonds, e.g. foscarnet, trichlorfon
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/10—Anthelmintics
Definitions
- the present invention relates to compositions for controlling parasites, comprising a combination of ivermectin, abamectin, albendazole sulphoxide and trichlorfon and the use of such compositions in the preparation of a medicament for controlling parasites.
- Endoparasites commonly cause clinical disease in especially in livestock animals and have significant adverse economic effects on farming economies when present at subclinical levels.
- the most frequently encountered endoparasites are the group of worms referred to as nematodes.
- the nematodes are found in the intestinal tract, heart, lungs, blood vessels and other body tissues of animals and are a primary cause of anemia, weight loss and malnutrition in the infected animals.
- the nematodes most commonly found to be the infecting agents of ruminants include Haemonchus and Ostertagia generally found in abomasum; Cooperia, Trichostrongylus and Nematodirus generally found in the intestinal tract, and Dictyocaulus found in the lungs.
- the resistance occurs when a strain of a parasite is able to tolerate doses of an active ingredient that is efficacious against other populations of parasites of the same species. This characteristic is inheritable.
- Avermectins are well known anthelmintic compounds, belonging to the class of macrocyclic lactones.
- the avermectins are isolated from fermentation products of Streptomyces avemitilis and ivermectin is a compound which is a semisynthetic chemical compound formed by modification of avermectin.
- the basic structure of the avermectins is a 16-membered lactone ring to which are appended three main substituent groups: a hexahydrobenzofuran group, a disaccharide group (at C-13) and a spiroketal ring (C-17 to C-28).
- the avermectin series of compounds including ivermectin, abamectin, doramectin, eprinomectin and selamectin, are potent anthelmintic and antiparasitic agents against internal and external parasites (endectocides).
- avermectins are disclosed in US-A-4,310, 519 to Albers Schonberg et al., and the 22,23-dihydro avermectin compounds are disclosed in Chabala et al, US-A- 4,199, 569.
- Albendazole sulphoxide (also known as ricobendazole) is a benzimidazole carbamate which is used as a broad spectrum anthelmintic in veterinary medicine.
- the preparation and certain uses of albendazole sulphoxide are disclosed in U.S. Pat. No. US 3,915,86. It is also the metabolite of two other veterinary drugs: netobimin and albendazole.
- Albendazole is the generic name for [5-(propylthio)-1 H- benzimidazol-2-yl)]carbamic acid methyl ester.
- the preparation and certain uses of albendazole are disclosed in U.S. Pat. No. 3,915,986.
- Trichlorfon (O,O-dimethyl-(2,2,2-trichloro-1-hydroxyethyl)-phosphonale dimethyl 2,2,2,2-trichloro-1-hydroxyethyl-phosphonate, also called metrifonate is an organophosphorous compound having potent anticholinesterase activity and is administered topically as an ectoparasiticide or orally as an anthelmintic.
- Organophosphates as antiparasitic agents are e.g. dichlorvos, coumaphos, crufomate or haloxon.
- Organophosphates act as cholinesterase inhibitor by irreversible inactivation of acetylcholinesterase, leading to excessive cholinergic activity at relevant sites.
- the present invention concerns an anthelmintic composition, which comprises a combination of ivermectin, abamectin, albenazole sulphoxide and trichlorfon.
- the present invention provides an antiparasitic composition, which comprises as active ingredient, an effective amount of a combination of ivermectin, abamectin, albendazole suphoxide and trichlorfon in the following concentrations: 0.02-1.0% or 0.05- 0.25% w/w ivermectin, 0.01-0.5%, or 0.05-0.25% w/w abamectin, 0.3 - 15%, or 1.0% - 2.5% w/w albendazole sulphoxide and 10-70 %, or 15- 60% w/w trichlorfon.
- the invention includes pharmaceutically acceptable salts of the compounds.
- Pharmacologically intolerable salts which can initially be obtained, for example, as process products in the production of the compounds according to the invention on the industrial scale, are converted into the pharmacologically tolerable salts by processes known to the person skilled in the art.
- the active ingredients may be present in the dosage form as true mixtures, but they may also be administered individually in separate dosage forms and form mixtures only when they are in the host animal.
- the pharmaceutical composition can be in a form suitable for oral or intraruminal administration, as a solid dosage form, a liquid suspension, or a paste.
- Conventional liquid formulations for oral administration are usually solutions, suspensions or emulsions of the active ingredients together with suitable diluents, solvents, flavours and colours to form a dosage form.
- the composition is in the form of a powder for extemporaneous suspension. This powder is suspended in water or in a suspension containing active ingredients before oral administration to the animal.
- the particular amount of the anthelminthic compound required for a particular treatment will vary, depending upon the species, age and weight of the animal being treated, the particular parasite to be guarded against, or treated, as well as the specific organophosphate compound selected for the treatment, the route and the frequency of administration. Anthelminthics are frequently delivered to ruminants in the form of oral drenches directly into the rumen.
- w/v weight/weight, i.e. “1 % w/v” means 1 g in 100 g of the composition, "v/v” means volume per volume, and 1% v/v means 1 ml, in a total of 100 ml.
- composition comprising 0.1% ivermectin, 0.05% abamectin, 20% trichlorfon and 1.5% albendazole sulphoxide.
- a recommended dosage is 2 ml of the aqueous suspension based on the powder formulation described above per 5 kg body weight of the animal.
- novel compositions according to the invention have proven good efficacy against internal parasites, especially in sheep and goats.
- the novel compositions according to the invention result in a unique formulation which controls parasites resistant to ivermectin and doramectin, like, Cooperia spp. and Haemonchus spp.
- compositions of the invention may be used for the preparation of a medicament for controlling parasites in and on host animals, particularly in ruminants such as sheep, cattle and goats.
- methylparaben methylparaben, propylparaben, sodium laurylsulfate or other wettable surfactant, aluminum hydroxide dry, Aerosil 200, albendazole sulphoxide, ivermectin and abamectin. Stir until getting homogeneous suspension. Trichlorfon is added at the moment of using.
- the following solid ingredients are introduced sequentially into a vessel containing water and with the stirring: methylparaben, propylparaben. Aerosil 200, albendazole sulphoxide, ivermectin and abamectin. Stir until getting homogeneous suspension and add the mixture of water, polysorbate, antifoam and ethanol. Trichlorfon is added at the moment of using.
- the combination according to the invention showed a egg per gram (e p g) reduction in sheep on Day 3 of 97.0 % compared with 84% for trichlorfon, 66.1 % for albendazole sulphoxide, 63.8% for ivermectin and 30% for abamectin alone.
- Efficacy on e.p.g. reduction in sheep was evaluated for the combination of 0.1 % ivermectin, 0.1% abamectin, 3% albendazole sulphoxide and either 20% or 25% trichlorfon compared with the commercial product TRIMIX of Merial containing 200 mcg/kg ivermectin, 7,5 mg/kg levamisole, 5 mg/kg albendazole .
- Trichlorfon showed a e.p.g. reduction in sheep on Day 3 of 99.5% % and 100% for Trichlorfon 25 % compared with 92.2% for TRIMIX.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Claims
Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
BRPI0820260-5A BRPI0820260A2 (en) | 2007-11-09 | 2008-11-07 | Anthelmintic composition and use of composition |
CN200880114965A CN101848710A (en) | 2007-11-09 | 2008-11-07 | Anthelmintic combination |
AU2008324095A AU2008324095A1 (en) | 2007-11-09 | 2008-11-07 | Anthelmintic combination |
MX2010004852A MX2010004852A (en) | 2007-11-09 | 2008-11-07 | Anthelmintic combination. |
ZA2010/02315A ZA201002315B (en) | 2007-11-09 | 2010-03-31 | Anthelmintic combination |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP07120380 | 2007-11-09 | ||
EP07120380.6 | 2007-11-09 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2009060063A1 true WO2009060063A1 (en) | 2009-05-14 |
Family
ID=39059330
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP2008/065126 WO2009060063A1 (en) | 2007-11-09 | 2008-11-07 | Anthelmintic combination |
Country Status (7)
Country | Link |
---|---|
CN (1) | CN101848710A (en) |
AR (1) | AR069223A1 (en) |
AU (1) | AU2008324095A1 (en) |
BR (1) | BRPI0820260A2 (en) |
MX (1) | MX2010004852A (en) |
WO (1) | WO2009060063A1 (en) |
ZA (1) | ZA201002315B (en) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2011027333A1 (en) * | 2009-09-07 | 2011-03-10 | Douglas Robert Cleverly | Granulated anthelmintic preparations and delivery systems |
WO2013095286A3 (en) * | 2011-12-20 | 2013-11-07 | Christer Edlund | Synergistic combination comprising avermectins and a nsaid for tumor inhibition |
RU2699799C1 (en) * | 2019-01-10 | 2019-09-11 | Федеральное государственное бюджетное учреждение науки Сибирский федеральный научный центр агробиотехнологий Российской академии наук (СФНЦА РАН) | Antiparasitic composition and a method for use thereof for treating parasitosis of ruminant animals |
CN114569561A (en) * | 2022-03-28 | 2022-06-03 | 中牧实业股份有限公司黄冈动物药品厂 | Albendazole ivermectin powder and preparation method and application thereof |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102743403A (en) * | 2012-06-26 | 2012-10-24 | 格特生物制药(天津)有限公司 | Parasite expelling tablet for domestic animals and preparation method thereof |
CN102726443B (en) * | 2012-07-12 | 2013-11-27 | 中国林业科学研究院亚热带林业研究所 | Ivermectin and dipterex compound pesticide |
CN113755610B (en) * | 2021-10-08 | 2023-09-12 | 内蒙古自治区农牧业科学院 | Gene for detecting sensitivity of haemonchus contortus to ivermectin and application |
CN114452314A (en) * | 2022-01-12 | 2022-05-10 | 河南百草元兽药有限公司 | Albendazole ivermectin powder and preparation method thereof |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1194832A (en) * | 1997-03-27 | 1998-10-07 | 王玉万 | Antiparasitic medicine containing avermectin/ivermectin for animals |
WO2004069242A1 (en) * | 2003-02-05 | 2004-08-19 | Jurox Pty Ltd | Anthelmintic composition |
-
2008
- 2008-11-07 AR ARP080104874A patent/AR069223A1/en unknown
- 2008-11-07 AU AU2008324095A patent/AU2008324095A1/en not_active Abandoned
- 2008-11-07 BR BRPI0820260-5A patent/BRPI0820260A2/en not_active IP Right Cessation
- 2008-11-07 MX MX2010004852A patent/MX2010004852A/en not_active Application Discontinuation
- 2008-11-07 WO PCT/EP2008/065126 patent/WO2009060063A1/en active Application Filing
- 2008-11-07 CN CN200880114965A patent/CN101848710A/en active Pending
-
2010
- 2010-03-31 ZA ZA2010/02315A patent/ZA201002315B/en unknown
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1194832A (en) * | 1997-03-27 | 1998-10-07 | 王玉万 | Antiparasitic medicine containing avermectin/ivermectin for animals |
WO2004069242A1 (en) * | 2003-02-05 | 2004-08-19 | Jurox Pty Ltd | Anthelmintic composition |
Non-Patent Citations (2)
Title |
---|
DATABASE CAPLUS [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; 2000, "Antiparasitic compositzions containing avermectin / ivermectin for veterinary use", XP002469864, retrieved from STN Database accession no. 2000:246638 * |
WRIGLEY J ET AL: "Resistance to a triple combination of broad-spectrum anthelmintics in naturally-acquired Ostertagia circumcincta infections in sheep.", NEW ZEALAND VETERINARY JOURNAL FEB 2006, vol. 54, no. 1, February 2006 (2006-02-01), pages 47 - 49, XP009110069, ISSN: 0048-0169 * |
Cited By (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2011027333A1 (en) * | 2009-09-07 | 2011-03-10 | Douglas Robert Cleverly | Granulated anthelmintic preparations and delivery systems |
AU2020202781B2 (en) * | 2009-09-07 | 2021-05-13 | Argenta Innovation Limited | Granulated anthelmintic preparations and delivery systems |
US11253593B2 (en) | 2009-09-07 | 2022-02-22 | Argenta Innovation Limited | Granulated anthelmintic preparations and delivery systems |
AU2022200149B2 (en) * | 2009-09-07 | 2023-06-15 | Argenta Innovation Limited | Granulated anthelmintic preparations and delivery systems |
WO2013095286A3 (en) * | 2011-12-20 | 2013-11-07 | Christer Edlund | Synergistic combination comprising avermectins and a nsaid for tumor inhibition |
AU2012354236B2 (en) * | 2011-12-20 | 2017-10-05 | Ectin Research Ab | Synergistic combination comprising avermectins and a NSAID for tumor inhibition |
US9782424B2 (en) | 2011-12-20 | 2017-10-10 | Ectin Research Ab | Synergistic combination comprising avermectins and a NSAID for tumor inhibition |
RU2699799C1 (en) * | 2019-01-10 | 2019-09-11 | Федеральное государственное бюджетное учреждение науки Сибирский федеральный научный центр агробиотехнологий Российской академии наук (СФНЦА РАН) | Antiparasitic composition and a method for use thereof for treating parasitosis of ruminant animals |
CN114569561A (en) * | 2022-03-28 | 2022-06-03 | 中牧实业股份有限公司黄冈动物药品厂 | Albendazole ivermectin powder and preparation method and application thereof |
Also Published As
Publication number | Publication date |
---|---|
MX2010004852A (en) | 2010-06-02 |
ZA201002315B (en) | 2010-11-24 |
AU2008324095A1 (en) | 2009-05-14 |
AR069223A1 (en) | 2010-01-06 |
BRPI0820260A2 (en) | 2015-05-26 |
CN101848710A (en) | 2010-09-29 |
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